The UCSD Cancer Center plans to develop a research program with the theme of mo1ecular approaches to prevention and treatment of breast cancer. The plan incorporates the advantages of a matrix interfacing site-oriented clinical programs with the established basic research programs of the Cancer Center, and also takes advantage of infrastructure recently put into place to facilitate translational research. The plan derives five pilot projects from several of the established programs of the Cancer Center: (1) from the Growth Control, Cancer Genetics, and Cancer prevention and Control programs, a project to develop and compare two new methods for surveying the entire tumor genome for abnormalities (representational difference analysis, and differential mRNA display). These comparisons will be on specimens from several studies, including a soon-to-be-initiated privately funded UCSD adjuvant dietary intervention project in women with localized breast cancer, the Long island case cluster, and material from the other projects in this proposal; (2) from the immunology program, a project to develop vaccines against neu peptides, initially from transgenic mammary tumors and later from human tumors; (3) from the Clinical investigation and Developmental Therapeutics (CIDT) program, an attempt to predict the eventual clinical response to chemotherapy of breast cancer, based upon the 24-hour post-treatment activation of tumor cell genes that respond to cellular injury e.g. gaddi53 and c-jun; (4) from the CIDT program and collaborations with investigators at Salk institute, a study to detect the presence of and results from elimination of amplified genes contained in double-minute chromosomes harbored within breast cancer cells from patients with chemotherapy-refractory disease; and (5) from the Cancer Genetics Program, a project using pseudotyped retroviral vectors carrying IL-2, GMCSF, and B7 genes to infect human breast cancers after completion of a pre-clinical feasibility study in nude mice. Funding support is requested for the pilot projects, including the recruitment of three new key investigators: a molecular biologist, a molecular cytogeneticist, and a molecular epidemiologist, and for administration and planning. It is anticipated these projects will develop into peer-review funded studies which will coalesce into the nucleus of a highly interactive site- oriented program. The cohesion, focus, multidisciplinary interaction, and productivity of the program will depend upon successful recruitment of the new investigators, the scientific and administrative competence of the P.I., Dr. William Hryniuk, and his standing as the Director of the UCSD Cancer Center. Success will also be fostered by input from the senior individuals comprising a program advisory committee, and reinforced by the substantial resources already committed to the breast program by UCSD School of Medicine, UCSD Medical Center, and affiliated institutions. The excellent basic science milieu of UCSD should sustain a high level of performance of participants in the program.